Chronic seropositive polyarthritis associated with hepatitis B virus-induced chronic liver disease: a sequel of virus persistence
Since Robert Graves' report (1) on a patient with acute polyarthritis followed by icteric hepatitis and urticaria, there has been a large body of evidence proving that hepatitis viruses can induce extrahepatic syndromes and conditions (2,3). While prodromal manifestations of acute viral hepatitis are usually selflimited, conditions associated with virus persistence can profoundly contribute to morbidity and mortality. Acute hepatitis B arthritis represents a polyarthritic syndrome affecting mainly the small joints, which tends to present in a symmetric pattern mimicking that of rheumatoid arthritis (RA) (4,5). Although glomerulonephritis, mixed cryoglobulinemia, and polyarteritis nodosa have been clearly established as possible consequences of hepatitis B virus (HBV) persistence (2,3), available data about the association between chronic polyarthritis and hepatitis B surface antigen (HBsAg) carrier state of HBV-related chronic liver disease are highly controversial (2-7).
We evaluated the clinical significance of HBV in patients with early RA (duration Յ12 months). Fifty patients (44 women, 6 men; mean age 54 years) without any previous history of chronic liver disease who were referred to our rheumatology department between 1996 and 1998 for evaluation of chronic polyarthritis were consecutively enrolled and studied by 2 of the authors (BR and GP). Informed consent was obtained from all patients prior to study enrollment. All patients fulfilled the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) criteria for RA (8) and showed clinically active disease, meeting at least 3 of the first 4 ACR criteria. Clinical evaluation included a tender joint count and swollen joint count (based on 68 joints and 66 joints, respectively, scored on a scale of 0-3), physician and patient overall assessment (100-mm visual analog scale), early morning stiffness, disability, and pain index measurement (by the Health Assessment Questionnaire [9]). Cases of infectious hepatitis and risk factors for viral hepatitis were also recorded. Serum samples were screened by one of the authors (MH), under blinded conditions, for serologic markers of HBV infection (HBsAg and anti-hepatitis B core antigen, third-generation enzyme immunoassay [EIA]; Abbott, Abbott Park, IL), as well as for antibodies to hepatitis C virus (HCV) (third-generation EIA; Abbott). Patients who had infectious hepatitis and/or had received multiple blood transfusions were also tested for markers of "waterborne" hepatitis viruses (hepatitis A and E). HBV DNA was quantified by the branched DNA method (Quantiplex; Chiron, Emeryville, CA). Rheumatoid factor (RF) was detected using the latex fixation and Rose-Waaler tests. Sera containing RF at a titer of Ն1:32 were regarded as positive. Levels of alanine aminotransferase (ALT), alkaline phosphatase, and bilirubin were also assessed.
Four patients (8%) had serologic marker(s) of HBV, and 2 of them were found to be HBsAg positive (Table ). Of interest, no serum was found to contain anti-HCV antibodies. Both of the HBsAg-positive patients displayed a typical presentation of RA, meeting the first 4 ACR criteria. Their sera